title: miR-381, a novel intrinsic WEE1 inhibitor, sensitizes renal cancer cells to 5-FU by up-regulation of Cdc2 activities in 786-O.
abstract: BACKGROUND
  Few researches on increase of chemotherapy sensitivity by microRNA (miRNA) were reported. We aim to investigate exact role of miR-381 in chemotherapy sensitivity of 5-fluorouracil (5-FU) in renal cancer cells.
  
  
  METHODS
  We investigated the cell survival, cell-cycle and apoptosis of 786-O and HK-2 cells treated with miR-381 and 5-FU. IC50 of 5-FU was calculated. To study apoptosis and G2/M arrest, we determined pHH3, mitotic index and caspase-3/7 activity.
  
  
  RESULTS
  We showed that miR-381 combined with 5-FU inhibited proliferation and potentiated the anti-tumour efficacies of 5-FU at tolerated concentration in vitro. miR-381 combined with 5-FU led to Cdc2 activation, mitotic catastrophe, and cell apoptosis through inhibitory WEE1. WEE1 was also validated as the direct target of miR-381. IC50 of 5-FU decreased significantly in the presence of miR-381.
  
  
  CONCLUSIONS
  miR-381 increases sensitivity of 786-O cells to 5-FU by inhibitory WEE1 and increase of Cdc2 activity.
authors.affiliation: Department of Urology, Third Xiang-Ya Hospital of Central South University, Changsha 410000, China.
authors.forename: Binghai
authors.initials: B
authors.lastname: Chen
authors.forename: Lujing
authors.initials: L
authors.lastname: Duan
authors.forename: Guangming
authors.initials: G
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000187:drug effects; D018844:Cyclin-Dependent Kinases; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D035683:MicroRNAs / Q000494:pharmacology* / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B; D035683:MicroRNAs; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D005472:Fluorouracil